Background. The injectable contraceptive progestagen, depot medroxyprogesterone acetate (DMPA), has been used worldwide by over 11 million women. Concerns exist about breast cancer risk, particularly following long-term use. Yet the few epidemiological studies carried out to date have not had the data to assess risk immediately following long- term use, or after a delay. It is also possible that in the short term DMPA may increase risk, and in the long term reduce it. Hypothesis. The study will assess whether DMPA use for 5= years increases (or decreases) breast cancer risk overall, or after a latent interval. It will also assess risk according to duration of exposure, and in subgroups (e.g., exposure in adolescence; risk according to age at occurrence of breast cancer). Methods. A hospital-based case-control study will be carried out in the Western Cape of South Africa. 382 African (i.e., black) and Colored (i.e., mixed ancestry) cases below age 55 will be compared with 1,528 controls frequency-matched for age, ethnic group and hospital. White women will be excluded because DMPA use among them is uncommon. Among potential controls preliminary investigations have established that over 30% have ever used DMPA; well over 10% have been exposed for 5+ years. These are the highest documented exposure rates in the world. Ont eh conservative assumption of 10% exposure for 5+ years, power will be at least 80% to document an increased (or decreased) relative risk of 1.5 (or 0.6); for breast cancer occurrence beyond age 40 (about 257 cases), the estimate is 1.8 (or 0.4).